Over the past 20 years, technological advances in molecular biology have
proven invaluable to the understanding of the pathogenesis of human cancer.
The application of molecular technology to the study of cancer has not only
led to advances in tumor diagnosis, but has also provided markers for the
assessment of prognosis and disease progression. The aim of Molecular Analysis
of Cancer is to provide a comprehensive collection of the most up-to-date
techniques for the detection of molecular changes in human cancer.

Upon mutation of Asn130 to aspartate, the catalytic activity of human
arginase I was reduced to17% of wild-type activity, theKmvalue for
arginine was increased9-fold, and thekcat
⁄Kmvalue was reduced50-fold. The kinetic properties were much less affected by replacement of
Asn130 with glutamine.

Recent studies on type II thioesterases (TEIIs) involved in
microbial secondary metabolism described a role for these
enzymes in the removal of short acyl-S- phosphopantetheine
intermediates from misprimed holo-(acyl carrier proteins)
and holo-(peptidyl carrier proteins) of polyketide synthases
and nonribosomal peptide synthetases.

Flavonols are produced by the desaturation of flavanols
catalyzed by flavonol synthase. The enzyme belongs to the
class of intermolecular dioxygenases which depend on
molecular oxygen and Fe
II
/2-oxoglutarate for activity, and
have been in focus of structural studies recently. Flavonol
synthase cDNAs were cloned from six plant species, but
none of the enzymes had been studied in detail.

The protonation state of residues around the Qo binding site of the cyto-chrome bc1 complex from Paracoccus denitrificansand their interaction
with bound quinone(s) was studied by a combined electrochemical and
FTIR difference spectroscopic approach. Site-directed mutations of two
groups of conserved residues were investigated: (a) acidic side chains
located close to the surface and thought to participate in a water chain
leading up to the heme bLedge, and (b) residues located in the vicinity of
this site. ...

Populations in Southeast AsiaandSouthChinahave highfrequencies ofa-thalassemia
caused by a-globin gene mutations and/or deletions. This study was designed to find
an efficient and simple diagnostic test for the mutations and deletions. A duplex polymerase
chain reaction (PCR)/denaturing high-pressure liquid chromatography
(DHPLC) was used to detect the mutations and deletions. A blinded study of 110
samples, which included 92 a-thalassemia samples with various genotypes and 18
normal DNA samples, was carried out by the methods.

Mitochondrial DNA (mtDNA) deletion mutations accumulate with age in tissues of a variety of species. Although the relatively low calculated abundance of these deletion mutations in whole tissue homogenates led some investigators to suggest that these mutations do not have any physiological impact, their focal and segmental accumulation suggests that they can, and do, accumulate to levels suﬃcient to aﬀect the metabolism of a tissue.

Chapter 7 - Anatomy and function of a gene: dissection through mutation. This chapter includes contents: Mutations: primary tools of genetic analysis, what mutations tell us about gene structure, what mutations tell us about gene function, a comprehensive example: mutations that affect vision.

Human topoisomerase I binds DNA in a topology-dependent fashion with
a strong preference for supercoiled DNAs of either sign over relaxed circu-lar DNA. One hypothesis to account for this preference is that a second
DNA-binding site exists on the enzyme that mediates an association with
the nodes present in supercoiled DNA.

Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM)
are the most common hereditary cardiac conditions. Both are frequent
causes of sudden death and are often associated with an adverse disease
course.Alpha-cardiac actinis one of the disease genes where different mis-sense mutations have been found to cause either HCM or DCM. We have
tested the hypothesis that the protein-folding pathway plays a role in dis-ease development for two actin variants associated with DCM and six asso-ciated with HCM....